The hypothesis is proposed that prostaglandin biosynthesis by breast cancers is stimulated by prolactin in tumors which are hormonally sensitive. This is based on evidence that prolactin stimulates prostaglandin production in normal murine mammary tissue. This hypothesis predicts the following experimental observations: 1) Prostaglandin concentrations should be higher in hormonally sensitive tumors; 2) Prolactin should stimulate prostaglandin production in hormonally sensitive tumors; 3) Estrogens should induce prostaglandin synthetase in hormonally sensitive breast tumors; or 4) Estrogens should increase the sensitivity of the prostaglandin synthetase system to prolactin in hormonally sensitive tumors. We plan to test these predictions using radioimmunoassay measurement of tissue prostaglandin E2, prostaglandin snthetase and phospholipase A2 activity in human breast tumors which are classified as hormonally sensitive by the presence of estrogen receptors and in DMBA induced rat mammary tumors which have been exposed to altered (elevated and/or lowered) levels of estrogen and/or prolactin. These latter manipulations will be accomplished by injection of estrogen, ovariectomy and injection of prolaction or administration of prolactin elevating or prolactin release inhibiting drugs.